ORPHANIN FQ OPIOID INTERACTIONS IN MODULATING SYNAPTIC PLASTICITY

孤啡肽-阿片类物质相互作用对突触可塑性的调节 1.为了进一步研究FQ对突触传递的影响， 和齿状回的LTP。将讨论以下问题： a. FQ抑制外侧和内侧穿支LTP吗 路径？ B.阿片肽能拮抗阿片类药物对LTP的易化作用吗？ 侧穿支径？ C. LTP的哪个阶段，诱导期还是维持期，受到干扰， FQ？ D.内源性FQ的调节是否在LTP的调节中起作用？ 确定FQ是否能拮抗阿片类药物诱导的去抑制作用。 a.在有LTP存在的情况下， GABAA拮抗剂？ B. FQ增强GABA能抑制性突触后电流 （IPSCs）的齿状颗粒细胞或促进IPSCs的LTP？ C. FQ能否作用于GABA能终末影响单突触IPSC 颗粒细胞吗 D.阿片肽FQ能拮抗阿片诱导的索马细胞超极化吗 齿状GABA能中间神经元。 e.齿状核GABA能中间神经元表达ORL-1吗？ 如果是，ORL-1免疫反应性的位置是否支持 FQ对中间神经元索马或其轴突的可能作用 终端？ 3.检测FQ对齿状回NMDA通道电流的抑制作用 颗粒细胞 a. FQ抑制NMDA受体介导的兴奋性突触后神经元的表达 电流（EPSCs）诱发的齿状颗粒细胞？ B. FQ抑制局部应用的细胞膜电流 NMDA？ 4.检测FQ是否减少突触前谷氨酸的释放。 a. FQ抑制红藻氨酸/AMPA受体介导的EPSCs， 改变颗粒细胞对局部应用的红藻氨酸盐的反应。 B. FQ是否能降低自发性微小EPSC的频率？ 颗粒细胞 C. FQ是否能减少K+诱导的，Ca2+依赖的谷氨酸， 海马切片。

Orphanin FQ-Opioid InteractIons in Modulating Synaptic Plasticity 1. To further examine the effect of orphanin FQ on synaptic transmission and LTP in the dentate gyrus. The following questions will be addressed; a. Does orphanin FQ inhibit LTP in both the lateral and medial perforant path? b. Can orphanin FQ antagonize m opioid-induced facilitation of LTP in the lateral perforant path? c. Which phase of LTP, induction or maintenance, is interfered by orphanin FQ? d. Does endogenous orphanin FQ play a role in the modulation of LTP? To determine if orphanin FQ can antagonize opioid-induced disinhibition. a. Can orphanin FQ inhibit synaptic transmission and LTP in the presence of GABAA antagonists? b. Does orphanin FQ enhance GABAergic inhibitory postsynaptic currents (IPSCs) of dentate granule cells or facilitate LTP of IPSCs? c. Can orphanin FQ act on GABAergic terminals to affect monosynaptic IPSCs of granule cells? d. Can orphanin FQ antagonize opioid-induced hyperpolarization at the soma of dentate GABAergic interneurons. e. Is ORL-1 immunoreactivity expressed by dentate GABAergic interneurons? If they are, does the location of ORL-1 immunoreactivity support a possible effect of orphanin FQ on the interneuron soma or their axon terminals? 3. To examine it orphanin FQ inhibits NMDA channel currents in dentate granule cells. a. Does orphanin FQ depress NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) evoked in dentate granule cells? b. Does orphanin FQ depress membrane currents induced by locally applied NMDA? 4. To examine if orphanin FQ reduces presynaptic glutamate release. a. Can orphanin FQ inhibit kainate/AMPA receptor mediated EPSCs without changing granule cell responses to locally applied kainate. b. Does orphanin FQ reduce the frequency of spontaneous miniature EPSCs in granule cells. c. Can orphanin FQ reduce K+-induced, Ca2+ -dependent glutamate from hippocampal slices.